Naturally Derived Membrane Lipids Impact Nanoparticle-Based Messenger RNA Delivery
- PDF / 1,587,826 Bytes
- 12 Pages / 593.972 x 792 pts Page_size
- 25 Downloads / 204 Views
Cellular and Molecular Bioengineering ( 2020) https://doi.org/10.1007/s12195-020-00619-y
2020 CMBE Young Innovators issue
Naturally Derived Membrane Lipids Impact Nanoparticle-Based Messenger RNA Delivery JEONGHWAN KIM,1 ANTONY JOZIC,1 and GAURAV SAHAY
1,2
1
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Robertson Life Sciences Building, Portland, OR, USA; and 2Department of Biomedical Engineering, Oregon Health Science University, Robertson Life Sciences Building, Portland, OR, USA (Received 17 February 2020; accepted 16 May 2020) Associate Editor Michael R. King oversaw the review of this article.
Abstract Introduction—Lipid based nanoparticles (LNPs) are clinically successful vectors for hepatic delivery of nucleic acids. These systems are being developed for non-hepatic delivery of mRNA for the treatment of diseases like cystic fibrosis or retinal degeneration as well as infectious diseases. Localized delivery to the lungs requires aerosolization. We hypothesized that structural lipids within LNPs would provide features of integrity which can be tuned for attributes required for efficient hepatic and non-hepatic gene delivery. Herein, we explored whether naturally occurring lipids that originate from the cell membrane of plants and microorganisms enhance mRNA-based gene transfection in vitro and in vivo and whether they assist in maintaining mRNA activity after nebulization. Methods—We substituted DSPC, a structural lipid used in a conventional LNP formulation, to a series of naturally occurring membrane lipids. We measured the effect of these membrane lipids on size, encapsulation efficiency and their impact on transfection efficiency. We further characterized LNPs after nebulization and measured whether they retained their transfection efficiency. Results—One plant-derived structural lipid, DGTS, led to a significant improvement in liver transfection of mRNA. DGTS LNPs had similar transfection ability when administered in the nasal cavity to conventional LNPs. In contrast, we found that DGTS LNPs had reduced transfection efficiency in cells pre-and post-nebulization while maintaining size and encapsulation similar to DSPC LNPs. Conclusions—We found that structural lipids provide differential mRNA-based activities in vitro and in vivo which also depend on the mode of administration. Understanding influence of structural lipids on nanoparticle morphology
Address correspondence to Gaurav Sahay, Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Robertson Life Sciences Building, Portland, OR, USA. Electronic mail: [email protected]
and structure can lead to engineering potent materials for mRNA-based gene therapy applications. Keywords—Lipid nanoparticles, Structural lipid, Gene delivery.
ABBREVIATIONS DSPC
1,2-Distearoyl-sn-glycero-3-phosphocholine DGTS 1,2-Dipalmitoyl-sn-glycero-3-O-4¢(N,N,N-trimethyl)-homoserine MGDG Monogalactosyldiacylglycerol DGDG Digalactosyldiacylglycerol SQDG Sulfoquinovosyldiacylglycerol Cyclo PC 1-Palmitoyl-2-cis-9
Data Loading...
